PMID- 25078894
OWN - NLM
STAT- MEDLINE
DCOM- 20150302
LR  - 20220309
IS  - 1553-7358 (Electronic)
IS  - 1553-734X (Print)
IS  - 1553-734X (Linking)
VI  - 10
IP  - 7
DP  - 2014 Jul
TI  - Algorithms to model single gene, single chromosome, and whole genome copy number 
      changes jointly in tumor phylogenetics.
PG  - e1003740
LID - 10.1371/journal.pcbi.1003740 [doi]
LID - e1003740
AB  - We present methods to construct phylogenetic models of tumor progression at the 
      cellular level that include copy number changes at the scale of single genes, 
      entire chromosomes, and the whole genome. The methods are designed for data 
      collected by fluorescence in situ hybridization (FISH), an experimental technique 
      especially well suited to characterizing intratumor heterogeneity using counts of 
      probes to genetic regions frequently gained or lost in tumor development. Here, 
      we develop new provably optimal methods for computing an edit distance between 
      the copy number states of two cells given evolution by copy number changes of 
      single probes, all probes on a chromosome, or all probes in the genome. We then 
      apply this theory to develop a practical heuristic algorithm, implemented in 
      publicly available software, for inferring tumor phylogenies on data from 
      potentially hundreds of single cells by this evolutionary model. We demonstrate 
      and validate the methods on simulated data and published FISH data from cervical 
      cancers and breast cancers. Our computational experiments show that the new model 
      and algorithm lead to more parsimonious trees than prior methods for single-tumor 
      phylogenetics and to improved performance on various classification tasks, such 
      as distinguishing primary tumors from metastases obtained from the same patient 
      population.
FAU - Chowdhury, Salim Akhter
AU  - Chowdhury SA
AD  - Joint Carnegie Mellon/University of Pittsburgh Ph.D. Program in Computational 
      Biology, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of 
      America; Lane Center for Computational Biology, Carnegie Mellon University, 
      Pittsburgh, Pennsylvania, United States of America.
FAU - Shackney, Stanley E
AU  - Shackney SE
AD  - Intelligent Oncotherapeutics, Pittsburgh, Pennsylvania, United States of America.
FAU - Heselmeyer-Haddad, Kerstin
AU  - Heselmeyer-Haddad K
AD  - Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, United 
      States of America.
FAU - Ried, Thomas
AU  - Ried T
AD  - Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, United 
      States of America.
FAU - Schaffer, Alejandro A
AU  - Schaffer AA
AD  - Computational Biology Branch, NCBI, NIH, Bethesda, Maryland, United States of 
      America.
FAU - Schwartz, Russell
AU  - Schwartz R
AD  - Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, 
      Pennsylvania, United States of America; Department of Biological Sciences, 
      Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.
LA  - eng
GR  - R01 AI076318/AI/NIAID NIH HHS/United States
GR  - 1R01AI076318/AI/NIAID NIH HHS/United States
GR  - R01 CA140214/CA/NCI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - 1R01CA140214/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20140731
PL  - United States
TA  - PLoS Comput Biol
JT  - PLoS computational biology
JID - 101238922
SB  - IM
CIN - New Methods Section in PLOS Computational Biology.
MH  - Algorithms
MH  - Breast Neoplasms
MH  - Computational Biology/*methods
MH  - Computer Simulation
MH  - DNA Copy Number Variations/*genetics
MH  - Databases, Genetic
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - *Models, Genetic
MH  - Neoplasms/*classification/*genetics
MH  - Uterine Cervical Neoplasms
PMC - PMC4117424
COIS- Dr Shackney is an employee of Intelligent Oncotherapeutics. All other authors 
      declare that no competing interests exist.
EDAT- 2014/08/01 06:00
MHDA- 2015/03/03 06:00
PMCR- 2014/07/31
CRDT- 2014/08/01 06:00
PHST- 2014/02/02 00:00 [received]
PHST- 2014/06/04 00:00 [accepted]
PHST- 2014/08/01 06:00 [entrez]
PHST- 2014/08/01 06:00 [pubmed]
PHST- 2015/03/03 06:00 [medline]
PHST- 2014/07/31 00:00 [pmc-release]
AID - PCOMPBIOL-D-14-00205 [pii]
AID - 10.1371/journal.pcbi.1003740 [doi]
PST - epublish
SO  - PLoS Comput Biol. 2014 Jul 31;10(7):e1003740. doi: 10.1371/journal.pcbi.1003740. 
      eCollection 2014 Jul.